Schematic protein domain structure of NR2F-family members. (A) Nuclear receptor gene family and its phylogenetic tree (source: nuclear receptor resource; John P. Vanden Heuvel, http://nrresource.org) (B) The common domain structures of NR2F1, NR2F2 and NR2F6 from the amino- to the carboxyl-terminus are indicated: the amino-terminal activation function 1 (AF1) domain (also called the A/B region), the central, highly conserved, DNA-binding-domain (DBD) (also called the C region), the hinge region (also called the D region), the ligand-binding domain (LBD) (also called the E region) and the activation function 2 (AF2) domain (also called the F region) and their relative positions. Briefly, the DNA binding domain (DBD), also called C region, of the different mammalian NR2F-family members is highly homologous between different species, which indicated the importance of this critical region for the biological function of these proteins . The A/B region, which is highly variable among different nuclear receptors, is located amino-terminal to the DBD domain. In general, this domain may contain ligand-independent transcriptional activity. The second most conserved region is the ligand binding domain (LBD) or E region, which is responsible for recognition and binding of the receptor’s ligand and for the ligand-dependent transcriptional activity. A relatively short region connects the C region to the E region (region D) and is also known as the hinge domain. Some receptors also contain a region that is carboxy-terminal to the ligand binding domain, which is known as the F region [1, 13, 18, 97].